The annual economic burden of the opioid epidemic is in excess of $78.5 billion.¹ High rates of opioid prescribing in the late 1990s and early 2000s have been credited with fueling this public health emergency.^2,3 Exposure to opioids through a legitimate prescription is frequently reported by individuals who go on to develop opioid use disorders and those transitioning to heroin use.^4,5 Though provisional data released by the CDC indicate that drug overdose deaths dropped for the first time since 1990,⁶ deaths due to opioids have continued to increase in SC, with 816 opioid-involved overdose deaths reported in 2018, a 9% increase from the prior year.⁷

Several factors have been identified as risk factors for prescription opioid overdose. A dose-response relationship between prescribed daily morphine milligram equivalents (MME) and risk for drug overdose has been demonstrated, with doses over 90 – 100 MME/day commonly identified as “high-risk.”^8,9 Second, use of high-dose, extended release/long acting (ER/LA) opioids for opioid naïve patients is associated with overdose risk.^10,11,12 Third, co-prescribing opioids and benzodiazepines increases risk of respiratory depression and overdose, with some evidence suggesting that concomitant use may increase risk of overdose by 4 to 12 times that of low-dose, lone opioid use. ^10,13,14 Finally, multiple prescribers in the same time frame may indicate diversion and is associated with overdose. Over the past decade, public health efforts to monitor prescriptions and increase prescriber coordination have been instituted as a method to address high-risk prescribing, doctor shopping, and diversion.^15,16,17,18

Although numerous individual studies have leveraged administrative claims data to estimate opioid prescribing indicators, many of these studies have been limited by only capturing a segment of opioids prescribed, representing prescriptions from a single healthcare system or single payer such as commercially insured, Medicaid, or Medicare only.^19,20 More complete data is made available annually by the Centers for Disease Control and Prevention, which produces prescribing maps that show the geographic distribution of retail opioid prescriptions dispensed per 100 persons between 2006 and 2016 for each state (and county) within the US.²¹ The source for all CDC prescribing data is the QuintilesIMS Transactional Data Warehouse, which is based on a sample of approximately 59,000 retail pharmacies which dispense almost 88% of all retail prescriptions paid for by commercial insurance, Medicaid, Medicare, or cash in the US.²¹ Perhaps the most complete data regarding the dispensation of opioid prescriptions are the state-operated prescription drug monitoring programs (PDMPs).

This study examines longitudinal trends for SC PDMP indicators defined by the Centers for Disease Control and Prevention (CDC) for their Prescription Drug Overdose Prevention for States surveillance program.²² For the years 2010 through 2018, we report trends in the SC PDMP reflecting: (1) number and rate of opioid analgesic prescriptions dispensed per 1,000 state residents; (2) percent of patients receiving opioids dispensed an average daily dose ≥ 90 MME; (3) percent of opioid prescribed days with overlapping opioid and benzodiazepine prescriptions; (4) rate per 100,000 residents of multiple provider episodes; and, (5) percent of patients prescribed ER/LA opioids who were opioid-naive.

A total of 33,027,461 opioid prescriptions were filled within the time period. The number of opioid analgesics per 1,000 state residents decreased significantly over the study period (Figure 1), with a 41% drop in quarterly prescribing rate from Q1 2010 to Q4 2018 (p=0.0001). Figure 2 shows the percent of opioid prescribed patients receiving an average daily dose of ≥90 MME of opioid analgesics, percent of opioid naïve patients prescribed ER/LA opioids, percent of prescription days with overlapping opioid and benzodiazepine prescriptions, and rate of multiple provider episodes per 100,000 residents. Each indicator decreased significantly over the study period (p≤0.005 for all) by 23%, 31%, 35%, and 92%, respectively.

The current study reports trends in opioid prescribing over the most recent decade (2010 – 2018) derived from a uniquely comprehensive, statewide PDMP database. PDMP data represent perhaps the most complete information on opioid prescriptions. Our findings show that the volume of dispensed opioid prescriptions in SC decreased by more than 41% between 2010 and 2018. This dramatic reduction was accompanied by significant decreases in all four high-risk prescribing indicators: 1) high daily MMEs; 2) co-prescribing opioids and benzodiazepines; 3) number of multiple prescriber episodes; and 4) percent of patients prescribed ER/LA opioids who were opioid-naive.

Across the US and Canada, recent data suggest declining rates for both the number of people prescribed opioids as well as the number of physicians prescribing opioids.^23,24 Consistent with trends observed in the current data, the CDC report of annual data from IQVIA Xponent national administrative claims data indicated that total number of prescriptions peaked nationally in 2012 and has subsequently declined; however, prescribing rates continue to remain high in certain areas of the country and vary widely across different states and counties.²¹ SC annual rates of opioid prescribing from IQVIA data indicate a 19.6% decrease from 2010 (98.6) to 2017 (79.3). A larger 41% decrease in quarterly prescribing rate for the same timeframe was found in the comprehensive PDMP data.

Our results are also consistent with findings from several administrative claims databases showing general decreases in high-risk prescribing indicators including: multiple provider episodes, incidence of initial opioid prescriptions among opioid naïve individuals, proportion of persons receiving high (>90 MME) daily doses, number of extended release opioid prescriptions, and co-prescription of benzodiazepines.^{25,26,27,28,29} The most notable declines were evinced for multiple provider episodes. Though the current data cannot speak to mechanisms or drivers of this stark decline, findings suggest that PDMPs may be particularly useful in assisting in the identification of “doctor shopping” or diversion. Of note, national data pulled from IQVIA (2006 through 2017) indicate that while trends in high-risk prescribing hold when examined nationally, between 2 to 3-fold variations in these outcomes were observable by state.²⁸

PDMPs may be valuable clinical tools for informing and monitoring opioid prescribing and are an important risk mitigation strategy to help reverse the prescription opioid drug epidemic by promoting more conservative prescribing practices. Several multi-pronged efforts to increase PDMP use were undertaken in SC to address high rates of opioid prescribing. These efforts included: (1) Revised Joint Pain Management Guidelines (November 2014 revision incorporated PDMP use as mandatory for safe pain treatment, August 2017 revision aligned with CDC Guidelines); (2) addition of data from major Veterans Administration hospitals to PDMP (December 2014); (3) integration of PDMP data into electronic health records (EHRs) for two initial emergency department sites (September 2015); (4) online PDMP registration for prescribers (November 2015); (5) insurer/payer mandates for PDMP use (spring 2016); (6) SC PreSCriptions – Medication Safety Matters statewide initiative (launched September 2016); (7) legislative mandate for PDMP use prior to prescribing Schedule II controlled substance (spring 2017); and (8) Academic Detailing to Primary Care Providers, including hands on PDMP training (launched June 2017).

The current study cannot definitively attribute decreases in overall and high risk prescribing to any specific intervention(s); however, efforts reflected in this state are common across the U.S. For example, as of 2017, 22 states had at least one type of MME Daily Dose policy in place, most commonly in the form of guidelines (14 states), followed by: prior authorizations, rules and regulations, legislative acts, claim denials, and automatic patient reports.³⁰ The literature regarding impact of specific PDMP-related interventions is mixed. Data (2010–2015) from the state PDMPs of Ohio, Kentucky, and West Virginia were recently compared to control states.³¹ Reports show that mandatory PDMP use laws increased prescriber registration and utilization of the PDMP in mandated states compared with non-mandated states. The rate of opioid prescribing, rate of overlapping prescriptions, multiple provider episode rate, and rate of overlapping opioid/benzodiazepine prescriptions decreased in 2 of 3 states evaluated; however, magnitude of these changes varied among mandated states. In contrast, a recent systematic review did not find evidence to support an association between PDMPs (policy and use) and reduced opioid prescribing and dispensing.³²

The current study has limitations. First, our analysis is limited to a single state and may not be representative of other states; opioid prescribing varies widely across the US^28,33 and patterns of high-volume opioid prescribing vary by drug type and region of the US.³⁴ Second, while there is inherent public health value in monitoring trends in opioid prescribing we cannot measure the clinical appropriateness of reductions in prescribing. Third, tramadol was excluded from the indicators presented in this study since tramadol prescriptions were not consistently reported in PDMP data until its reclassification in August 2014. The data available 2015 – 2018 indicate that though tramadol prescription rates were high (ranging from 824,585 to 964,501 prescriptions per year), their inclusion in analyses did not substantially alter the prescribing trends reported in this study. Finally, while missing/unusable data is very small it has potential for biasing our results.

Our results indicate that public health policy and legislative action aimed at reducing high rates of opioid prescribing are bearing fruit. However, it is critical that future research examines more granular issues regarding the drivers and impact of reductions in opioid prescribing. For example, recent data suggest that, independent of absolute opioid dose, high dose variability is associated with a significantly increased risk of overdose compared with low dose variability.³⁵ Future research should examine more nuanced aspects of opioid prescribing practices, including: which prescriber types drive overall reductions in opioid prescriptions; provider-level correlates of reduced prescribing; clinical appropriateness of prescribing reductions; impact of prescribing reductions on patients’ access to care; and potential negative impacts on patient care and safety.